Precision modification of the human gut microbiota targeting surface-associated proteins

Area of Science:

• Microbiology
• Immunology
• Biotechnology

Background:

• The human gut microbiota plays a crucial role in health and disease.
• Understanding the specific functions of individual bacterial species within complex communities is challenging.
• Targeted manipulation of the gut microbiota is essential for therapeutic interventions.

Purpose of the Study:

• To develop a novel antibody-based method for the targeted modification of the human gut microbiota.
• To specifically identify and deplete Lactobacillus acidophilus from complex microbial communities.
• To lay the groundwork for precision microbiome-based therapies.

Main Methods:

• Development of a polyclonal antibody against the Surface Layer Protein A of Lactobacillus acidophilus DSM20079^T.
• Conjugation of antibodies with fluorescent probes and magnetic particles for identification.
• Application of flow cytometry for bacterial detection and depletion.
• Optimization of the depletion procedure using a trypsin step for selective isolation.

Main Results:

• Successfully identified Lactobacillus acidophilus in synthetic and real gut microbiota using antibody-conjugated probes.
• Demonstrated the ability to deplete Lactobacillus acidophilus from complex human gut microbiotas in a single step.
• Observed co-depletion of interacting bacterial species, indicating community interactions.
• Achieved selective and complete isolation of Lactobacillus acidophilus after procedural optimization.

Conclusions:

• Antibody-mediated, flow cytometry-based targeting offers a novel approach for precise gut microbiota editing.
• This method facilitates research into the immunomodulatory and metabolic contributions of specific bacteria.
• The developed technique provides a foundation for developing precision microbiome-based therapeutic strategies.